Recombinant human erythropoietin dosing errors due to concentrated EPO.

AIMS: Recombinant human erythropoietin (rHuEPO) is widely used to treat anemia. A dialysis provider enacted a policy utilizing 20,000 U/ml multi-dose vials for rHuEPO dosing. The purpose of this study was to determine the accuracy and precision in administering small rHuEPO doses from this vial. METHODS: Ten registered nurses (RNs) were selected at random, supplied with a rHuEPO vial refilled with water, and instructed to withdraw the following amounts (1,200 U, 2,400 U, 3,600 U) using standard procedures and assuming the standard rHuEPO concentration of 20,000 U/ml. Samples were drawn up in duplicate and placed into 1.5 ml micro-centrifuge tubes. The volumes were measured using P-100 or P-200 microliter pipettes. The equivalent amount of rHuEPO was calculated by multiplying the volume by 20 U/microl. RESULTS: The rHuEPO dosing errors were large and on occasion greater than 100% at the 1,200 U dose. The variability for each RN, while large, was less than the inter-RN variability (within-RN % error 9.6% vs. 29.8% between-RN % error at the 1,200 unit dose). Errors occurred in both directions, both under- and overdosing. CONCLUSION: Utilizing concentrated rHuEPO resulted in significant dosing errors at low rHuEPO doses. The implications include inaccurate medication administration and disparity between administered and billed dosages. Policy decisions that effect medication administration need to be carefully evaluated to determine their impact on patient well-being and safety.

Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients.

The risk of death in hemodialysis patients treated with calcium-containing phosphate binders or sevelamer is not known. We assessed all-cause mortality in 127 patients new to hemodialysis assigned to calcium-containing binders or sevelamer after a median follow-up of 44 months from randomization. This was a predetermined secondary end point of a randomized clinical trial designed to assess progression of coronary artery calcium (CAC) scores in the two treatment arms. Thirty-four deaths occurred during the follow-up period: 23 in subjects randomized to calcium-containing phosphate binders and 11 in subjects randomized to sevelamer. Baseline CAC score was a significant predictor of mortality after adjustment for age, race, gender, and diabetes with increased mortality proportional to baseline score (P=0.002). Mortality was borderline significantly lower in subjects randomized to sevelamer (5.3/100 patient years, confidence interval (CI) (2.2-8.5) compared to those randomized to calcium-containing binders (10.6/100 patient years, CI 6.3-14.9) (P=0.05). The greater risk of death for patients treated with calcium-containing phosphate binders persisted after full multivariable adjustment (P=0.016, hazard ratio 3.1, CI 1.23-7.61). In subjects new to hemodialysis baseline CAC score was a significant predictor of all-cause mortality. Treatment with sevelamer was associated with a significant survival benefit as compared to the use of calcium-containing phosphate binders.

Comparison of cuffed tunneled hemodialysis catheter survival.

Despite efforts to have hemodialysis patients begin renal replacement therapy with a mature arteriovenous shunt, many patients begin dialysis with a cuffed tunneled catheter as their access. An increasing number of differently designed tunneled hemodialysis catheters have become available in the last decade. The primary aim of this study is to compare catheter survival for Hickman (Bard, Salt Lake City, UT) and Opti-flow (Bard) catheters. The 16-month experience with 182 catheters, totaling 13,861 catheter-days, is reported. The probability of Hickman catheter failure at 30, 60, and 90 days was 29%, 49%, and 67%. The probability of Opti-flow catheter failure was significantly less at 10%, 24%, and 38% for the same times, respectively (P: < 0.05 for all time points). The difference in catheter failure rates was caused by a greater malfunction rate of Hickman catheters; the two catheters had similar infection rates. We conclude that survival of Opti-flow catheters was significantly better than that of Hickman catheters from 30 to 90 days, which is a clinically relevant period when patients are waiting for maturation of a permanent access or replacement of a failed access. Since the conclusion of our study, we documented 10 episodes of Opti-flow catheter malfunction within 4 months secondary to hairline fracture of the arterial hub. The Opti-flow catheter was recalled and is now available with retooled hubs.

Bioimpedance resistance ratios for the evaluation of dry weight in hemodialysis.

MATERIAL: Restoration of body water compartments to normal by ultrafiltration is a major goal of hemodialysis. Dry weight is the term used to define normal body water in dialysis patients, but it is limited, as it is based solely on clinical observations. Bioimpedance spectroscopy can accurately measure the resistance of body fluid compartments. The ratio of the resistances of the intracellular to extracellular water should reflect the relative volume of these compartments. As dialysis patients accumulate excess fluid in their extracellular compartment, this ratio may prove useful in the evaluation of dry weight. METHODS: We measured the resistances of the intracellular and extracellular fluid compartments in normal subjects to define the normal ratio of the resistances of these compartments. Women had a slightly higher ratio than men (women: 2.41 +/- 0.23 vs. men: 2.08 +/- 0.23 vs. p < 0.0001). The ratios determined in the normal population were taken as the normal physiologic ratio and were used to define physiologic dry weight. We then compared dialysis patients both pre- and post-dialysis to this normal population. RESULTS: We found that most patients (67%, n = 18) had an elevated ratio pre-dialysis suggesting excess extracellular fluid. Of the 38 treatments in which patients achieved their clinical dry weight, 19 (50%) had persistently elevated Ri/Re ratios, suggesting they had not reached physiologic dry weight. CONCLUSION: These data suggest that many dialysis patients carry excess extracellular fluid post dialysis despite achieving their clinical dry weight. Furthermore, the resistance ratio derived from bioimpedance spectroscopy may be a useful clinical tool in determining dry weight.

The effect of hemodialysis on cycloserine, ethionamide, para-aminosalicylate, and clofazimine.

STUDY OBJECTIVES: Determine hemodialysis clearances of the second-line antitubercular drugs cycloserine (CS), ethionamide (ETA), para-aminosalicylate (PAS), and clofazimine (CFZ). DESIGN: Open-label, pharmacokinetic study SETTING: Outpatient long-term hemodialysis unit PARTICIPANTS: Eight long-term hemodialysis patients Interventions: Single oral doses of CS, 500 mg, ETA, 500 mg, PAS, 4,000 mg, and CFZ, 200 mg, were given 2 h (4 h for PAS) prior to hemodialysis (median blood flow rate, 400 mL/min; median dialysate flow rate, 600 mL/min; median hemodialysis time, 3.5 h). MEASUREMENTS AND RESULTS: Arterial and venous serum samples were collected at the beginning and end of hemodialysis, and hourly during hemodialysis. Dialysate fluid was collected for the duration of hemodialysis. All samples were assayed for drug concentrations using validated high-performance liquid chromatography (for ETA and PAS), capillary electrophoresis (for CS), and colorimetry (for CFZ). Dialysate samples were analyzed for acetyl-PAS. Median recoveries of drug in dialysate were 56% (CS), 2.1% (ETA), 6.3% (PAS parent compound), and 0% (CFZ) of the doses administered. Acetyl-PAS was dialyzed to a greater extent than its parent compound. Median hemodialysis clearances calculated by dividing the amount recovered in dialysate by the serum area under the curve during dialysis were 189 (CS), 58 (ETA), 206 (PAS), and 0 (CFZ) mL/min. CONCLUSIONS: ETA, CFZ, and PAS were not significantly dialyzed. CS is significantly removed by hemodialysis and should be dosed after hemodialysis.

The effect of hemodialysis on isoniazid, rifampin, pyrazinamide, and ethambutol.

This study examines hemodialysis clearances of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Seven chronic hemodialysis patients were studied. Six were given single oral doses (INH 300 mg, RIF 600 mg, PZA 1000 mg, and EMB 25 mg/kg) 2 h before hemodialysis (Cobe Centrysystem 3 hemodialysis machine; Fresenius F80B dialyzer; median blood flow rate 400 ml/min; dialysate flow rate 600 ml/min; median hemodialysis time 3.5 h). The seventh subject, being treated for tuberculosis (TB), was studied with his usual regimen. Arterial and venous serum samples were collected at the beginning and end of hemodialysis, and hourly during hemodialysis. Dialysate was collected for the duration of hemodialysis. All samples were assayed for drug concentrations using high-performance liquid chromatography (HPLC) (INH, RIF) and gas chromatography/mass spectrometry (GC/MS) (PZA, EMB) methods. Median recoveries of drug in dialysate were 9% (INH), 4% (RIF), 45% (PZA), and 2% (EMB) of the doses administered. Median hemodialysis clearances calculated by dividing the amount recovered in dialysate by the serum area under the curve during hemodialysis were 124 (INH), 40 (RIF), 270 (PZA), and 46 (EMB) ml/min. INH, RIF, and EMB were not significantly removed by hemodialysis. PZA is significantly dialyzed and should be dosed after hemodialysis.

Assessment of excess fluid distribution in chronic hemodialysis patients using bioimpedance spectroscopy.

Sodium and water homeostasis is abnormal in hemodialysis (HD) patients, however, the distribution of the excess fluid (extracellular vs. intracellular) has not been fully characterized. We studied the distribution of fluid using bioimpedance spectroscopy to determine if HD patients have an excess of fluid in any specific compartment relative to controls. Dual-energy x-ray absorptiometry was used to measure lean body mass and bone mineral content. The resistive index (RI) for extracellular water volume (RIECW), was significantly increased in patients pre-HD when corrected for bone mineral content (RIECW:BMC) (pre-HD, 19.0 +/- 3.3; controls, 15.8 +/- 1.7 cm2-ohms(-1)-kg -1; P < 0.01). This value decreased to the control range following HD (15.2 +/- 2.5 cm2-ohms(-1)-kg(-1). The intracellular water volume to bone mineral content (RIICW:BMC) was not different between controls and HD patients. These data suggest that hemodialysis patients carry their excess fluid volume primarily in the extracellular compartment and that bioimpedance spectroscopy coupled with a stable measure of lean tissue such as bone mineral content can determine the degree of relative excess hydration.

Hemodialysis urea rebound: the effect of increasing dialysis efficiency.

Urea rebound has been documented to occur after hemodialysis, but the magnitude and causes are not clearly defined. In this study we evaluated the effect of high-flux hemodialysis on urea rebound and Kt/V. Blood urea nitrogen samples were obtained before, immediately after, and 30 minutes after hemodialysis in 49 patients. Rebound was evaluated with respect to dialysis efficiency, dialysis treatment time, the occurrence of hypotension, and hematocrit. Urea rebound was significant and resulted in an overall decrease in Kt/V from 1.2 +/- 0.3 to 1.0 +/- 0.2 (P < 0.001). Of the 45 patients with a measured Kt/V of greater than 1.0, 40% had an actual delivered Kt/V of less than 1.0 once rebound was taken into account. Urea rebound correlated strongly with dialysis efficiency but not with hypotension, suggesting that rebound resulted primarily from delayed urea mass transfer across cell membranes. We conclude that increasing dialysis efficiency increases urea rebound and increases the error in Kt/V determinations from single pool urea kinetics.

Serum albumin: a predictor of long-term outcome in peritoneal dialysis patients.

We report a long-term follow-up of 71 peritoneal dialysis patients who participated in a prior study that evaluated the serum albumin concentration as a predictor of short-term morbidity. In this study the use of the original serum albumin level to predict failure of peritoneal dialysis or death was investigated. Sixty-nine of the original 71 study patients were followed for 2 years from the time of enrollment in the initial study. Patients who died within this 2-year period had a significantly lower serum albumin concentration during the original study period (2.7 +/- 0.7; n = 8) than those remaining on peritoneal dialysis (3.6 +/- 0.4, n = 31), those transferred to hemodialysis (3.4 +/- 0.5; n = 13), or those receiving renal transplants (3.6 +/- 0.4 g/dL; n = 17) (P < 0.05 for all comparisons v the group that died). A low serum albumin during the original study period was not predictive of patients who transferred to hemodialysis. We conclude that the stable outpatient serum albumin concentration in peritoneal dialysis patients is a powerful predictor of mortality as well as of short-term morbidity.

Serum albumin: a marker for morbidity in peritoneal dialysis patients.

This study was designed to determine if the serum albumin is a marker for morbidity or mortality in peritoneal dialysis (PD) patients. The impact of a low serum albumin on the risk of hospitalization, peritonitis, or death was examined in 71 patients. Blood urea nitrogen (BUN), cholesterol, age, and the presence or absence of diabetes were also examined. In independent analyses, the serum albumin was lower (32.7 +/- 5.6 v 36.3 +/- 4.3 g/L, P < 0.01), the diagnosis of diabetes was more frequent (41% v 7%, P < 0.01), and the number of episodes of peritonitis were greater (2.0 +/- 1.6 v 0.7 +/- 1.3, P < 0.01) in the group of patients hospitalized compared with those not hospitalized. When diabetics were excluded from analysis, the serum albumin remained significantly lower in hospitalized patients. Stepwise logistic regression analysis, excluding the 10 patients hospitalized only for treatment of peritonitis, confirmed that only a low serum albumin and the diagnosis of diabetes were independent predictors of increased morbidity as evident by the increased frequency of hospitalization. Every 10 g/L decrease in the serum albumin increased the odds ratio for hospitalization by 5.2. The diagnosis of diabetes resulted in a 10-fold increase in the odds ratio. We conclude that a low serum albumin serves as a marker of morbidity in PD patients, primarily as a marker of increased risk for hospitalization. The diagnosis of diabetes also greatly increases the likelihood of hospitalization. Peritonitis is a cause for hospitalization, but not an independent risk factor.

The effect of prestorage irradiation on posttransfusion red cell survival.

Transfusion-associated graft-versus-host disease (TA-GVHD) may occur whenever immunologically competent allogeneic lymphocytes are transfused to an immunocompromised recipient. Irradiation of blood components eliminates the risk of TA-GVHD but may damage the cellular elements in the transfused component, particularly if the cells are stored for prolonged periods in the irradiated state. To study the effect of irradiation on long-term storage of red cells, AS-1 red cells from eight normal subjects were prepared on two occasions. On one occasion, the units were stored as standard AS-1 red cells for 42 days at 4 degrees C; on the other, they were exposed to 3000 cGy radiation within 4 hours of collection and then were stored as AS-1 red cells for 42 days at 4 degrees C. The donations were at least 12 weeks apart. Irradiated units demonstrated significant elevations in poststorage plasma hemoglobin (Hb) (623 +/- 206 vs. 429 +/- 194 g/dL [6230 +/- 2060 vs. 4290 +/- 1940 g/L], p less than 0.02) and plasma potassium (78 +/- 4 vs. 43 +/- 9 mEq/L [78 +/- 4 vs. 43 +/- 9 mmol/L], p less than 0.01) and significant decreases in red cell ATP (1.9 +/- 0.2 vs. 2.1 +/- 0.3 microM/g Hb, p less than 0.04) and 24-hour posttransfusion red cell recovery (68.5 vs. 78.4%, p less than 0.02), as compared to nonirradiated units. It can be concluded that irradiation with 3000 cGy damages red cells and that long-term storage in the irradiated state may enhance this damage. Red cells should not be stored for 42 days after irradiation with 3000 cGy.

Serum amyloid P component: a predictor of clinical beta 2-microglobulin amyloidosis.

Beta 2-microglobulin (beta 2M) amyloidosis is common in patients on long-term hemodialysis, but the clinical conditions associated with disease activity are poorly understood. This study was designed to determine if the serum amyloid P (AP) component concentration is predictive of beta 2M amyloid disease activity. Serum AP component concentrations were determined by rocket immunoelectrophoresis and beta 2M concentrations by a commercially available kit. Radiographic evidence of beta 2M amyloidosis was determined from bone films of the hips, shoulders, and hands. Serum AP component concentrations were not different in dialysis and control patients. However, AP component concentrations in long-term (greater than or equal to 5 years) dialysis patients were significantly lower than in short-term (less than 5 years) dialysis patients (43.0 +/- 16.9 micrograms/mL [n = 28] v 56.0 +/- 18.3 micrograms/mL [n = 31], P less than 0.05). The patients on hemodialysis for 5 or more years who had radiographic evidence of severe beta 2 M amyloidosis were significantly older (57.9 +/- 9.5 v 38.3 +/- 11.3 years, P less than 0.001) and their serum AP concentrations were significantly lower (34.3 +/- 15.0 v 50.1 +/- 15.6 micrograms/mL, P less than 0.05) than long-term dialysis patients without radiographic evidence of disease. Stepwise regression analysis showed that the patient's age and serum AP component concentration were predictors of radiographic evidence of beta 2 M amyloidosis. Thus, serum AP component concentrations are decreased in long-term dialysis patients, suggesting accelerated deposition into amyloid deposits.(ABSTRACT TRUNCATED AT 250 WORDS)

Deposition and removal of cutaneous beta 2-microglobulin.

These studies were designed to track the cutaneous deposition of beta 2-microglobulin (beta 2M) in patients on chronic hemodialysis, patients with chronic renal insufficiency and patients with successful renal transplants. Immunoperoxidase staining of skin biopsies from dialysis patients demonstrated significantly increased amounts of beta 2M compared to controls (p < 0.01). There was a strong positive correlation between the skin beta 2M content and the years of dialysis treatment. Renal transplant recipients had decreased skin content of beta 2M compared to hemodialysis patients. There was no difference in the skin beta 2M content in patients with chronic renal insufficiency not on hemodialysis and controls. No dialysis patient had amyloid in the skin by Congo red stain. We conclude that beta 2M accumulates in the skin of patients on chronic hemodialysis. This beta 2M is not in the form of amyloid. Successful renal transplantation allows for the removal of beta 2M from the skin indicating that beta 2M not in the form of amyloid can be mobilized from tissue sites.

Air-exposed urine dipsticks give false-positive results for glucose and false-negative results for blood.

Urine dipstick jars often are left uncapped, which led the authors to wonder what effect prolonged air exposure might have on dipstick accuracy. Unexpired Ames Multistixs (Miles Inc., Elkhart, IN) were exposed to ambient air for intervals of up to eight weeks and were used to test urine for the presence or absence of blood, protein, and glucose. Multistixs were read by a blinded participant. A urine sample reading negative for glucose with unexposed (control) Multistixs tested trace positive with three of three Multistixs exposed for 7 days, and 1+ (three of six) or trace positive (three of six) (P less than 0.05) with Multistixs exposed for 28 days. A urine sample reading 1+ for blood with controls tested negative with five of six (P less than 0.05) and six of six (P less than 0.05) Multistixs exposed for 28 and 56 days, respectively. Protein detection was accurate up to 56 days. The authors conclude that urine dipstick jars should be recapped to avoid prompting needless evaluations of glucosuria or delaying detection of important causes of microscopic hematuria.

Calcium and phosphorus fluxes during hemodialysis with low calcium dialysate.

We evaluated the acute effects of varying dialysate calcium concentration on plasma concentrations and dialyzer fluxes of calcium and phosphorus in adult hemodialysis patients. Seven individuals with stable end-stage renal failure were dialyzed 4 hours, three times weekly. The effects of dialysates containing 1.75, 1.25, or 0.75 mmol/L (70.1, 50.1, or 30.1 mg/L) of calcium were compared. Each patient was studied once at each bath calcium concentration. Compared with the predialysis mean value of 2.27 mmol/L (9.1 mg/dL), plasma total calcium concentration increased, remained constant, or decreased with the 1.75-, 1.25-, or 0.75-mmol/L calcium dialysates, respectively. The 0.75-mmol/L calcium dialysate did not cause signs or symptoms of hypocalcemia (and the plasma calcium concentration did not fall below 1.80 mmol/L [7.2 mg/dL]). Plasma phosphorus concentrations decreased equally from a predialysis mean value of 2.16 mmol/L (6.7 mg/dL), regardless of the dialysate calcium concentration. After 4 hours of treatment with the three different dialysates, the cumulative calcium fluxes were significantly different. With 1.75 mmol/L calcium, mean bodily calcium accumulation was 21.9 mmol (879 mg). With 1.25 mmol/L, there was no net calcium flux. With 0.75 mmol/L, mean patient calcium loss was 5.8 mmol (231 mg). Mean phosphorus removal after 4 hours was 32.5 mmol (1,006 mg) and was unaffected by dialysate calcium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Determinants of survival and recovery in acute renal failure patients dialyzed in intensive-care units.

The survival rate of critically ill patients who develop acute renal failure is extremely low, in spite of the sophisticated support systems, including dialysis. Therefore, it would be advantageous to identify, early in the disease course, those few survivors. We reviewed the clinical course of 43 consecutive critically ill patients who developed acute renal failure and were first dialyzed in an intensive-care unit setting to define comorbid conditions, present at the time of first dialysis, that were predictive of outcome. Mortality rate was 88%. Adult respiratory distress syndrome (p less than 0.05), requirement for antibiotics (p less than 0.01) and ventilatory failure (p less than 0.01) impacted negatively on recovery of renal function. The most powerful predictor of mortality was the need for ventilatory support (p less than 0.001). The presence of ventilatory failure at the initiation of dialysis predicted a 100% mortality (89-100%; 95% confidence limits). The initiation of dialysis in intensive-care unit patients with acute renal failure requiring ventilatory support did not alter the uniformly fatal outcome.